Working nights may shift biological balance toward breast cancer

Jobs that require working in the wee hours of the night may do more than disrupt sleep and social lives. Recent studies suggest that women who work late-night shifts are at an increased risk of breast cancer. Researchers in the Public Health Sciences Division believe night-shift work may alter reproductive hormone levels in women, shifting the balance toward cancer. To test this theory, female nocturnal workers are being recruited for a first-of-its-kind study to see if such changes in hormonal levels can be detected.

Exposure to light at night can disrupt the body's production of melatonin, a brain hormone best known for its daily role in resetting the body's biological clock. Made at night by part of the brain known as the pineal gland, melatonin is believed to trigger a host of biochemical activities, including the body's production of estrogen. Some researchers think that chronically interfering with the body's nightly production of melatonin through exposure to light might increase risk of breast cancer. The Shift Worker Study (SWS) was launched in 2003 to see if disrupting a person's normal circadian rhythm (24-hour "biological clock") through night-shift work reduces the rise in melatonin that normally occurs at night.

Many animal studies have shown that disruption of melatonin production can affect ovarian function and the production of hormones particularly related to breast-cancer risk, such as estrogen, which may increase circulating levels of estrogen. Increased estrogen may promote breast cancer. Even tiny slivers of light at night have disrupted the melatonin levels of rats, promoting tumor growth.

The findings may explain why nurses who often work the night shift have high rates of breast cancer. The many unanswered questions surrounding melatonin have piqued the interest of Hutchinson Center scientists. "This study is a great opportunity to better pinpoint how a factor like working at night might actually be biologically related to the development of something as serious as breast cancer," said Dr. Scott Davis, principal investigator of the study.

The SWS is one of several projects conducted in the past decade looking at the effects of magnetic fields and light at night on breast cancer risk by Davis and his colleagues in the Radiation/Environmental Exposure Studies group. One of his earlier studies found that shift work was a significant predictor of increased risk of breast cancer. However, the findings didn't reveal what aspect of shift work heightened risk, nor were there any biological measures to prove hormonal changes.

To better understand how consistent late-night hours may affect reproductive hormone levels, study participants — hospital and laboratory employees — are asked to track their menstrual cycles and use an ovulation test kit for two months. Some study members also collect an optional blood or saliva sample. The second part of the study involves collecting urine for specific periods, wearing a watch-like device that measures movement during sleep, and for the night-shift workers, recording body temperature on certain days. Study staff conduct the visits and interviews in the participants' homes and retrieve the urine samples.

In addition to looking at the urinary concentration of reproductive hormones, the researchers are tracking particular characteristics of the participants' sleep patterns, which may be related to the hormone patterns identified. There are also specific genes known to regulate the circadian clock, so the study leaders are watching for certain gene alterations which affect a person's ability to adapt to shift work and may make a person more or less susceptible to the effects of working at night.

Recruitment goals

Christy Callahan, field operations coordinator for the study, says that recruitment of 200 night-shift and 150 day-shift workers has been challenging, but she estimates recruitment goals will be met in about two years.

"It's a complicated study to do in terms of field work," Davis said. "It also requires a lot from the participants, which is one of the reasons we focused on recruiting nurses and people in medical settings. They're used to collecting urine specimens and that sort of thing."

"We've found that people who work at night are very interested in this whole idea of how and why their work hours might affect health. They're eager to help. There's a general awareness of the potential health impact and an interest in trying to pursue this area as a scientific investigation."

There is considerable evidence that working at night can have deleterious effects on health. Various health conditions other than cancer have been associated with night-shift work, including a number of gastrointestinal disorders, depression, emotional distress, some cardiovascular events and adverse pregnancy outcomes.

Davis' group is currently pursuing funding to create a similar study in male night-shift workers. "We would focus on male reproductive hormones as they relate to prostate cancer," he said. "If these effects exist, there's no reason they would be limited to women. There could be a whole variety of potential health impacts." If hormone-level shifts are detected in either gender, Davis is hopeful that such identification could lead to follow-up interventions, recommendations and prevention guidelines.